CELL INTELLIGENCE · 肿瘤细胞治疗研究

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy is highly active in relapsed/refractory multiple myeloma (RRMM), but manufacturing creates an obligatory waiting period between apheresis and infusion. Patients may deteriorate, progress or die during this window. Analyses that begin follow-up at infusion exclude these patients entirely and cannot describe the experience of all patients who enter the CAR-T pathway. AIM: To describe, in an intention-to-collect fashion, the outcomes of all RRMM patients who underwent T-cell apheresis for planned CAR-T therapy; to characterise the apheresis-to-infusion interval and the reasons for, and correlates of, failure to reach infusion; and to report progression-free survival (PFS) and overall survival (OS) anchored at the date of apheresis. The study was descriptive; it was not designed to estimate the causal effect of CAR-T infusion on survival. METHODS: Retrospective single-centre cohort of all RRMM patients undergoing T-cell apheresis for CAR-T at Hackensack University Medical Center between 1 January 2021 and 30 April 2024. PFS and OS were calculated from apheresis by the Kaplan-Meier method with Greenwood 95% confidence intervals (CIs) and numbers at risk. Groups were compared with the log-rank test; baseline characteristics with the Wilcoxon rank-sum and Fisher exact tests. Because infusion is a post-baseline, time-dependent event, the association between infusion and survival was additionally examined using a Mantel-Byar time-dependent Cox model and a 60-day landmark analysis. Correlates of non-infusion were examined by univariable logistic regression; multivariable modelling was not performed owing to the small number of events. RESULTS: Of 99 patients undergoing apheresis, 87 (87.9%, 95%CI: 79.8-93.6) were infused and 12 (12.1%, 95%CI: 6.4-20.2) were not. Median follow-up was 14.0 months [interquartile range (IQR): 8.2-20.7]. Median apheresis-to-infusion interval was 54 days (IQR 46-62; range 37-202; n = 84 evaluable). Contrary to our preliminary report, baseline disease phenotype differed significantly between groups: Extramedullary disease was present in 9/12 (75.0%) non-infused vs 17/87 (19.5%) infused patients ( P < 0.001), and plasma cell leukaemia in 3/12 (25.0%) vs 3/87 (3.4%) ( P = 0.017). Age, prior lines of therapy (median 5 in both), high-risk cytogenetics (36.4% vs 34.1%) and Revised International Staging System distribution did not differ. The commonest reasons for non-infusion were progressive disease or myeloma-related death (7/12, 58.3%), non-myeloma death (2/12, 16.7%), manufacturing or collection failure (2/12, 16.7%) and infection (1/12, 8.3%). The median time from apheresis to the attrition event was 44 days (IQR 30-72). Median PFS from apheresis was 17.5 months (95%CI: 12.7-21.6) in infused patients vs 1.5 months (95%CI: 0.8-2.3) in non-infused patients; median OS was not reached vs 1.9 months (95%CI: 1.0-6.2) (both log-rank P < 0.001). In the time-dependent Cox model the hazard ratio for death associated with infusion was 0.24 (95%CI: 0.11-0.53), substantially closer to the null than the unadjusted comparison, illustrating how much of the apparent difference reflects the time-dependent nature of the exposure and confounding by disease phenotype. CONCLUSION: In this descriptive cohort, roughly one in eight patients who underwent apheresis never received CAR-T, and attrition clustered before the median time to infusion and among patients with extramedullary disease or plasma cell leukaemia. These data support shortening manufacturing turnaround, prioritising patients with aggressive phenotypes for expedited slots and intensified bridging, and reporting outcomes from apheresis using analytic methods that respect the time-dependent nature of infusion.